Abstract：
:During the development of multicellular organisms, concerted actions of molecular signalling networks determine whether cells undergo proliferation, differentiation, death or ageing. Here we show that genetic inactivation of the stress signalling kinase, MKK7, a direct activator of JNKs in mice, results in embryonic lethality and impaired proliferation of hepatocytes. Beginning at passage 4-5, mkk7(-/-) mouse embryonic fibroblasts (MEFs) display impaired proliferation, premature senescence and G2/M cell cycle arrest. Similarly, loss of c-Jun or expression of a c-JunAA mutant in which the JNK phosphorylation sites were replaced with alanine results in a G2/M cell-cycle block. The G2/M cell-cycle kinase CDC2 was identified as a target for the MKK7-JNK-c-Jun pathway. These data show that the MKK7-JNK-c-Jun signalling pathway couples developmental and environmental cues to CDC2 expression, G2/M cell cycle progression and cellular senescence in fibroblasts.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Wada T,Joza N,Cheng HY,Sasaki T,Kozieradzki I,Bachmaier K,Katada T,Schreiber M,Wagner EF,Nishina H,Penninger JMdoi
10.1038/ncb1098keywords:
subject
Has Abstractpub_date
2004-03-01 00:00:00pages
215-26issue
3eissn
1465-7392issn
1476-4679pii
ncb1098journal_volume
6pub_type
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